Combination vaccines with serogroup B meningococcus and D/T/P

Abstract

Serogroup B meningococcus antigens can successfully be combined with diphtheria, tetanus and pertussis toxoids (“DTP”) to provide effective combination vaccines for protecting against multiple pathogens. These combinations are effective with a range of different adjuvants, and with both pediatric-type and booster-type DTP ratios. The adjuvant can improve the immune response which the composition elicits; alternatively, by including an adjuvant it is possible for the compositions to have a relatively lower amount of antigen while nevertheless having immunogenicity which is comparable to unadjuvanted combination vaccines.

The invention claimed is: 
     
       1. An immunogenic composition, comprising: (a) a recombinant or purified serogroup B meningococcus immunogen, wherein the serogroup B meningococcus immunogen comprises a meningococcal factor H binding protein (fHbp) or a polypeptide having at least 85% sequence identity to SEQ ID NO: 4 or SEQ ID NO: 19; (b) a diphtheria toxoid, a tetanus toxoid, and a pertussis toxoid, wherein the tetanus toxoid is present in an excess relative to diphtheria toxoid as measured in Lf units; and (c) an adjuvant, wherein the adjuvant comprises an oil-in-water emulsion. 
     
     
       2. The composition of  claim 1 , further comprising in component (a) a Neisserial Heparin Binding Antigen (NHBA) protein or a polypeptide having at least 85% sequence identity to SEQ ID NO: 5 and a Neisserial adhesin A (NadA) protein or a polypeptide having at least 85% sequence identity to SEQ ID NO: 6. 
     
     
       3. The composition of  claim 1 , wherein the fHbp protein or the polypeptide is located in a meningococcal vesicle. 
     
     
       4. A method of raising an immune response in a mammalian subject, comprising the step of administering an effective amount of the composition of  claim 1  to the subject. 
     
     
       5. An immunogenic composition, comprising: (a) a recombinant or purified serogroup B meningococcus immunogen, wherein the serogroup B meningococcus immunogen comprises a meningococcal fHbp protein or a polypeptide having at least 85% sequence identity to SEQ ID NO: 4 or SEQ ID NO: 19; (b) a diphtheria toxoid, a tetanus toxoid, and a pertussis toxoid, wherein the tetanus toxoid is present in an excess relative to diphtheria toxoid as measured in Lf units; and (c) an adjuvant, wherein the adjuvant comprises an aluminium salt and a TLR agonist wherein the TLR agonist is adsorbed to the aluminium salt. 
     
     
       6. The composition of  claim 5 , wherein the adjuvant further comprises an oil-in-water emulsion. 
     
     
       7. The composition of  claim 5 , further comprising in component (a) a NHBA protein or a polypeptide having at least 85% sequence identity to SEQ ID NO: 5 and a NadA protein or a polypeptide having at least 85% sequence identity to SEQ ID NO: 6. 
     
     
       8. The composition of  claim 5 , wherein the fHbp protein or the polypeptide having at least 85% sequence identity to SEQ ID NO: 4 or SEQ ID NO: 19 is located in a meningococcal vesicle. 
     
     
       9. The composition of  claim 5 , wherein the TLR agonist is a TLR4 agonist, a TLR7 agonist, or a combination thereof. 
     
     
       10. The composition of  claim 9 , wherein the TLR agonist is a TLR7 agonist. 
     
     
       11. The composition of  claim 10 , wherein the TLR7 agonist is 3-(5-amino-2-(2-methyl-4-(2-(2-(2-phosphonoethoxy)ethoxy)ethoxy)phenethyl)benzo[f]-[1,7]naphthyridin-8-yl)propanoic acid, or a salt thereof.